Addressing Preeclampsia with Nanomedicine and Bioengineering
Marnie Winter and Benjamin Thierry from the University of South Australia, together with Tina Bianco-Miotto, Claire Roberts, and Clare Whitehead of the University of Adelaide in Australia and the University of Toronto in Canada, will develop and test short-interfering RNAs (siRNA) high-density lipoprotein (HDL) nanocarriers for the treatment of preeclampsia. Globally, ten million women develop preeclampsia during pregnancy each year, which results in the deaths of 76,000 women and 500,000 babies; 99% of these are in developing countries. Most current treatments focus on treating the symptoms (high blood pressure and proteinuria) rather than the molecular causes. Some of the causative molecules, such as the angiogenesis inhibitor sFlt1, can be blocked by specific siRNAs, but the challenge is targeting the siRNAs to the right cells in the body. HDL delivery systems for this purpose are effective and safe, and both siRNAs and HDLs are stable at room temperature, important for therapies in resource-poor areas. They will optimize the formulation of their HDL nanocarrier manufacturing platform, and characterize siRNA loading, carrier stability, size, cellular uptake, and silencing ability in 2D culture. Further, they will bioengineer an ex-vivo placenta model that fully recapitulates the structural and phenotypic complexity of a preeclamptic placenta and use it to evaluate tissue penetration and silencing abilities of the siRNA-nanocarrier complex.